Radioprotective effects of combination broncho‐vaxom, a macrophage activator, and indomethacin, an inhibitor of prostaglandin production: relationship to myelopoiesis

Abstract

The effects of the bacterial extract broncho‐vaxom (BV; radioprotective immunomodulator; 500 μg/mouse i.p., 24 h) and indomethacin (INDO; inhibitor of prostaglandin production; 2 times 40 μg/mouse i.m., ‐ 24 h and ‐ 3 h) on the post‐irradiation recovery of hemopoietic functions in mice were investigated. Both agents were administered either alone or in combination. Endogenous spleen colony formation was increased in all treatment groups, with combination‐treated mice exhibiting the greatest effects. Similarly, 24 h after combined administration of BV and INDO (i.e. at the time of presumed irradiation) to the non‐irradiated mice granulocyte‐macrophage colony‐forming cell (GM‐CFC) numbers were greater in the bone marrow and spleen. Also, as determined by hydroxyurea injection, there was an increase in the number of GM‐CFC in the S‐phase of the cell cycle in the bone marrow. However, GM‐CFC in the spleen of combination pretreated mice was not stimulated to significant proliferation as compared to GM‐CFC in the spleen of mice injected with BV alone. Combined modality treatment was also more effective than single agent treatments in accelerating bone marrow cellularity and GM‐CFC regeneration, but not in accelerating GM‐CFC regeneration in the spleen. Combined administration of BV and INDO to mice prior to lethal irradiation exerted an additional radioprotective effect and protected 95% of the C57B1/6 mice.

Development of Antioxidant COX-2 Inhibitors as Radioprotective Agents for Radiation Therapy—A Hypothesis-Driven Review

“…The combination with additional treatment strategies, namely administration of meloxicam and G-CSF or IB-MECA, an adenosine A 3 receptor agonist, increased the effect on hematopoiesis and survival rate in comparison to the treatment with each single drug [ 121 ]. A similar effect was observed for other NSAIDs as well; e.g., for indomethacin in combination with muramyl tripeptidephosphatidyl ethanolamine [ 122 ] or broncho-vaxom [ 123 ]. Meloxicam was investigated also in a glioblastoma multiforme tumor model because rapid recurrence of this malignancy after resection of the primary tumor has been related to the radiation induced stimulation of infiltration of glioma cells into healthy brain tissue and attributed partially to neuro-inflammatory processes.…”

Brief Story on Prostaglandins, Inhibitors of their Synthesis, Hematopoiesis, and Acute Radiation Syndrome

“…The results of these studies are presented in more detail in earlier reviews [2,55]. Briefly, non-selective COX inhibitors, like indomethacin, diclofenac, and flurbiprofen, were reported to enhance mouse hematopoiesis when administered singly before or after one-time-sublethal irradiation, in the course of fractionated irradiation [56,57,58], as well as when given concomitantly with immunomodulators [59,60,61] or chemical radioprotectors [62].…”

Appraisal of biochemical classes of radioprotectors: evidence, current status and guidelines for future development

“…It is assumed that understanding the mechanism of radioresistance and mimicking the condition may provide protection to humans against ionizing radiation. A few bacterial species are radioresistant (such as Deinococcus radiodurans, radiophilus, and grandis), and evidence suggests that extracts of those bacteria could confer radioprotective properties in different experimental models (Fedorocko and Mackova 1996;Daly et al 2010).…”